Cell therapy for myelodysplastic syndromes

Abstract

The invention provides methods for treating myelodysplastic syndrome (MDS). The invention is generally directed to reducing certain overt symptoms and disease-causing biological events in MDS by administering certain cells to a subject having MDS. The invention is also directed to drug discovery methods to screen for agents that modulate the ability of the cells to affect these events. The invention is also directed to cell banks that can be used to provide cells for administration to a subject, the banks comprising cells having desired potency for affecting these events.

What is claimed is: 
     
         1 . A method for treating a myelodysplastic syndrome, the method comprising administering cells to a subject having a myelodysplastic syndrome, wherein said cells are administered in sufficient quantity and for sufficient duration so as to treat one or more symptoms or biological events associated with the myelodysplastic syndrome, the cells being non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers. 
     
     
         2 . The method of  claim 1 , wherein the myelodysplastic syndrome is characterized by one or more of anemia, leukopenia, thrombocytopenia, or pathologically abnormal increase in blast cells. 
     
     
         3 . The method of  claim 2 , wherein administration of the cells produces a decrease in one or more of anemia, leukopenia, thrombocytopenia, or blast cells. 
     
     
         4 . A method for determining the efficacy of the method of any of  claims 1 - 3 , the method comprising post-administrative assessment of the effect of cellular treatment on one or more effects or symptoms of the myelodysplastic syndrome. 
     
     
         5 . The post-administrative diagnostic method of claim of  4 , wherein the efficacy of cellular treatment is measured based on the reduction of one or more of anemia, leukopenia, or thrombocytopenia in the subject. 
     
     
         6 . A method to assess the potency of a cell, the cell being a non-embryonic, non-germ cell that expresses one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers, the method comprising assaying for the potency of the cell to enhance differentiation, proliferation, or lifespan (viability) of red blood cells, leukocytes, platelets, or precursors of these cells. 
     
     
         7 . A method to increase the potency of a cell to enhance proliferation, differentiation, or viability of red blood cells, leukocytes, platelets or precursors thereof; the method comprising exposing the cell to an agent that increases that potency, the cell being a non-embryonic, non-germ cell that expresses one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers. 
     
     
         8 . A method comprising assessing cells for potency to cause increased proliferation, differentiation, or viability, of red blood cells, leukocytes, platelets, or precursors thereof, and, where the desired potency is found, administering said cells to a patient in sufficient numbers and for sufficient time to treat one or more symptoms or effects of a myelodysplastic syndrome, the cells being non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers. 
     
     
         9 . A method for treating a myelodysplastic syndrome in a subject, the method comprising selecting cells that have a desired potency for (1) differentiation of myeloid precursor cells, (2) proliferation of myeloid precursor cells, or (3) reducing apoptosis of myeloid precursor cells, the cells being non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers. 
     
     
         10 . A method for constructing a cell bank, said method comprising selecting cells that have a desired potency for (1) differentiation of myeloid precursor cells, (2) proliferation of myeloid precursor cells, or (3) reducing apoptosis of myeloid precursor cells; and expanding and storing the cells for future administration to a subject, the cells being non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers. 
     
     
         11 . A method for drug discovery, said method comprising selecting cells that have a desired potency for (1) differentiation of myeloid precursor cells, (2) proliferation of myeloid precursor cells, or (3) reducing apoptosis of myeloid precursor cells, the cells being non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of at least two of endodermal, ectodermal, and mesodermal germ layers. 
     
     
         12 . A method for establishing a therapeutic regimen in a subject with myelodysplastic syndrome, the method comprising (1) establishing a baseline in the subject for any of the following measurements: numbers of red blood cells, leukocytes, or platelets, administering cells in an amount and for a time sufficient to allow the cells to increase the numbers, assaying the subject for one or more of number of red blood cells, leukocytes, or platelets, wherein the cells that are administered are non-embryonic non-germ cells that express one or more of oct4, telomerase, rex-1 or rox-1 and/or can differentiate into cell type of at least two of endodermal, ectodermal, and mesodermal germ layers. 
     
     
         13 . A method for determining a therapeutically effective amount of cells administered to a subject, the cells being non-embryonic non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1, and/or can differentiate into cell types of at least two of endodermal, ectodermal, or mesodermal germ layers, the method comprising (1) assessing one or more in vive biomarkers, the biomarkers including, numbers of red blood cells, leukocytes, or platelets, following administration of the cells to the subject. 
     
     
         14 . The method of any of  claims 1 - 13  in which the cells are administered intravenously. 
     
     
         15 . The method of any of  claims 1 - 14  in which the symptom is anemia. 
     
     
         16 . The method of any of  claims 1 - 15 , in which the administered cells are allogeneic. 
     
     
         17 . The method of any of  claims 1 - 16 , in which the administered cells are non-embryonic, non-germ cells that express one or more of oct4, telomerase, rex-1, or rox-1 and/or can differentiate into cell types of all three of the endodermal, ectodermal, and mesodermal germ layers. 
     
     
         18 . The method of any of  claims 1 - 17 , in which the subject is human. 
     
     
         19 . The method of any of  claims 1 - 18 , in which the symptom is selected from the group consisting of infection, increased blood clotting time, and tiredness, and the effect is selected from the group consisting of numbers of red blood cells, leukocytes, or platelets.